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HBO-PC Promotes Locomotor Recovery by Reducing Apoptosis and Inflammation in SCI Rats: The Role of the mTOR Signaling Pathway

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Abstract

Hyperbaric oxygen preconditioning (HBO-PC) has beneficial effects on the promotion of locomotor recovery by reducing apoptosis and inflammation after traumatic spinal cord injury (SCI). The mammalian target of rapamycin (mTOR) signaling pathway has been implicated in apoptosis and inflammation in many pathophysiological conditions. However, whether HBO-PC improves traumatic SCI-induced locomotor dysfunction by regulating the mTOR signaling pathway and its downstream molecules remains unknown. In the present study, we found that HBO-PC significantly promoted SCI-induced hind-limb locomotor recovery and increased the amplitude and potential of motor evoked potential. Magnetic resonance imaging showed that spinal cavitation or atrophy caused by SCI was obviously alleviated by HBO-PC therapy. Histological analysis showed that the changes in spinal cord neural structure in SCI rats were markedly restored by HBO-PC treatment. Western blot analysis showed that the SCI-induced enhanced levels of p-mTOR, inflammatory cytokines and apoptosis in the spinal cord were abrogated after administration of HBO-PC. Furthermore, intrathecal administration of an mTOR agonist reversed the effects of HBO-PC on locomotor function recovery, p-NF-κB p65 and p-p70S6K levels, inflammation and apoptosis. These findings indicated a new mechanism by which HBO-PC therapy suppressed inflammation and apoptosis through inactivation of the mTOR signaling pathway, which contributed to motor disability in SCI rats.

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Funding

The study was supported by the Natural Science Foundation of Guangdong Province (No. 2017A030313693), the Research Program of PLA (No. CGZ16C004) and the Military Logistics Research Project (CN) (No. CWH17J022).

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Author notes

  1. Huiqiang Chen and Guoshen Xu contributed equally to this work.

Authors and Affiliations

  1. Department of Orthopedics, General Hospital of Southern Theater Command, Gusangzhou, 510010, Guangdong Province, China

    Huiqiang Chen, You Wu, Xinyu Wang, Fei Wang & Ying Zhang

  2. Department of Orthopedics, Guangdong Tongjiang Hospital, Foshan, 528300, Guangdong Province, China

    Guoshen Xu

Authors
  1. Huiqiang Chen
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  2. Guoshen Xu
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  3. You Wu
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  4. Xinyu Wang
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  5. Fei Wang
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  6. Ying Zhang
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Contributions

HC and YZ designed the study, and HC, GX, YW, XW and FW performed the experiments. HC and GX analyzed the data, and YZ wrote the manuscript. All authors read and approved the final manuscript.

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Correspondence to Ying Zhang.

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Ethical Approval

The experiments were performed in accordance with the guidelines of the General Hospital of Southern Theater Command Animal Ethics Committee. The protocol number is SYXK (Yue) 2019-0100.

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Chen, H., Xu, G., Wu, Y. et al. HBO-PC Promotes Locomotor Recovery by Reducing Apoptosis and Inflammation in SCI Rats: The Role of the mTOR Signaling Pathway. Cell Mol Neurobiol 41, 1537–1547 (2021). https://doi.org/10.1007/s10571-020-00921-3

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  • DOI: https://doi.org/10.1007/s10571-020-00921-3

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